Acumen Pharmaceuticals at UBS Virtual CNS Day: Alzheimer’s Treatment Focus

On Monday, 17 March 2025, Acumen Pharmaceuticals (NASDAQ: ABOS) presented at the UBS Virtual CNS Day 2025, focusing on their Alzheimer’s treatment, Subernatide. CEO Daniel O’Connor highlighted promising Phase 1 results and the potential of Subernatide as a selective monoclonal antibody. While enrollment in their Phase 2 study is ahead of schedule, challenges remain in differentiating their treatment in a competitive landscape.

Key Takeaways

• Acumen’s Phase 1 study demonstrated Subernatide’s safety and promising biomarker effects.
• Enrollment for the Phase 2 ALTITUDE-AD study is progressing faster than expected.
• Subernatide’s potential subcutaneous formulation aims to enhance patient access and convenience.
• Acumen plans to present further data at upcoming conferences, potentially boosting visibility.
• The company is exploring partnerships to advance its CNS treatment portfolio.

Operational Updates

Acumen’s Phase 2 study, ALTITUDE-AD, is enrolling patients faster than anticipated, with 540 participants involved in testing two active doses against a placebo. The Phase 1 study showed Subernatide’s safety, with low rates of ARIA, particularly in E4 homozygous patients. Acumen is also advancing a subcutaneous version of Subernatide, with results expected in Q1 2025.

Future Outlook

Acumen plans to complete enrollment for the ALTITUDE-AD study by the first half of 2025. The company is considering partnerships to accelerate Subernatide’s development into Phase 3. They are also focusing on the subcutaneous formulation to improve treatment accessibility.

Q&A Highlights

During the Q&A, O’Connor emphasized Acumen’s focus on amyloid beta oligomers and highlighted the promising results of Subernatide in reducing amyloid on PET scans. The Phase 2 dosing strategy is informed by Phase 1 data, aiming for optimal target engagement. The company reported low ARIA incidence, with only one symptomatic case among 48 subjects.

In conclusion, for more detailed insights, readers are encouraged to refer to the full transcript of the conference call.

Full transcript - UBS Virtual CNS Day 2025:

Operator: Welcome to the UBS virtual event. I would now like to pass the call over to Tron Huynh.

Trung Nguyen, Biopharma Analyst, UBS: Excellent. Thanks, Drew. And everyone who’s on, thanks for joining. So I have the honor of hosting the next session, the lunch slot for today’s virtual CNS day here at UBS. My name is Trung Nguyen.

I’m one of the biopharma analysts here. It’s my pleasure to welcome Daniel O’Connor, CEO of Acumen since 02/2014. Before that, he’s been a neuroscience for a number of years now, and forgive me if I’m making you sound old here, Dan, but over twenty years in value creation venture in, neurosciences. And he also cofounded functional neuromodulation, which was developing a a deep DBS, deep brain stimulation therapy in Alzheimer’s. So, Dan, thanks thanks for joining us today.

Daniel O’Connor, CEO, Acumen: Dan, thanks for the invitation. Great to see you.

Trung Nguyen, Biopharma Analyst, UBS: Awesome. So let’s start off with a quick intro for, those who don’t know what you’re doing over Acumen. Perhaps can you just describe where you are with Acumen today? And also, you know, I noted there you’ve been in neuroscience for a number of years, and Acumen is now a scientist company. But really that long term commitment to brain health, you know, it’s been a very tough area over the years.

There’s a lot of larger companies actually has deprioritized investment in this area. So perhaps why are you remaining so steadfast in this quite tricky area?

Daniel O’Connor, CEO, Acumen: Sure. Thanks, Chung. So I’ll just, firstly, I’ll start with Acumen. So at Acumen, we are singularly focused on, advancing novel treatments for people living with Alzheimer’s disease. That’s sort of our core area of focus.

Our clinical asset is, Subernatone, which is positioned as a next generation monoclonal antibody, based on its properties and ability to target what we think is a really optimal target in the disease pathology, which, we refer to as amyloid beta oligomers. And so, we can talk more on the data in support of that target as well as some of the phase one results for subirnatide that were reported out previously positive phase one results. In terms of the space, I think Acumen as a company, as an enterprise, just sees this unmet need and this massive opportunity to have an impact on this disease, which has been challenging to address over a number of years. We can sort of take the view that that that progress and knowledge and science and technology are cumulative. And that over the last fifteen years, we’ve actually developed better insights into which targets to pursue in this in this, disease population.

What technologies can better enable the accurate diagnosis and guide development paths. So, there’s a lot of reason, and now we have a couple of approved disease modifying treatments, the first couple products in the clinic today. And those are being adopted to the benefit of patients. But we think we can do more. I think what is exciting for me and for Acumen is the prospect of offering more quality time for people that otherwise have been diagnosed with an early Alzheimer’s diagnosis.

Trung Nguyen, Biopharma Analyst, UBS: So, yeah, you you touched upon here that there has been a glimmer of hope in the last couple of years. Lekembe, Kinsella now on the market after, I guess, October of r and d effort. But commercially, so far, they’ve not been as much of a success as some people had hoped for. So could you perhaps put your finger on why that’s the case? And then what are some of those clinical and commercial unmet needs you touched upon there that you think is still there beyond these first generations of products?

Operator: Sure, Trung. So, you know, in

Daniel O’Connor, CEO, Acumen: terms of the population in The US, there are somewhere in the order of seven million people that have, meet the criteria for early Alzheimer’s disease, which is mild cognitive impairment, and or dementia associated with with Alzheimer’s pathology. Those first two agents have been approved and and are essentially launched into a greenfield sites. There have been there haven’t been, established treatments for this particular disease, you know, heretofore. So, I think the commercial rollouts for these have been, haven’t met, the expectations of certain, stakeholders. But on the other hand, we’re seeing growth in terms of the script rates, and we’re seeing the infrastructure, the clinical infrastructure to actually diagnose and deploy these treatments for this population growing, incrementally, over time here.

What’s exciting for us is to be, you know, working on Subernatog and looking to read out a substantial proof of concept phase two study in the environment where, there’s more awareness and desire to have access to better treatment options. So the setup for us, I think, over the, you know, next two, three, four, five years is really compelling and one, again, where we’re focused on improving patient outcomes and improving patient lives.

Trung Nguyen, Biopharma Analyst, UBS: Okay. Awesome. And you touched upon the phase one data here. We’ve had some we’ve had that data for Sabernatag. It’s also a beta amyloid, so we’ve had much debate over this mechanism.

We have seen data readout for many beta amyloid. So with that data in hand, what gives you the confidence that this is the mechanism that’s gonna provide a meaningful benefit to Alzheimer’s disease patients. And, you also touched upon the oligomer side of things for Subernatag. Where why do you see that as differentiating, and what else could differentiate with your lead asset?

Daniel O’Connor, CEO, Acumen: Sure. So, a lot of questions embedded there. Let’s start with the complexity of A beta biology, which, you know, the amyloid precursor protein produces peptide fragments in a variety of different sizes and forms, But, that can take a variety of different species. So, we have A beta monomer, we have A beta oligomer, we have A beta protofibrils, and then plaques. And so, these different aggregated monomeric or aggregated forms, have different physiological effects.

I think a couple decades of research helped to underpin the notion that, or support the evidence for targeting A beta oligomers as a primary trigger in Alzheimer’s pathology and one that is a persistent, instigator and one that contributes to ongoing neurodegenerative processes. So, for instance, the A beta oligomers have been shown to induce tau hyperphosphorylation, that they have a propensity to bind to neurons and synapses and disrupt long term potentiation, which is the way, brain cells or neurons have the ability to communicate and essentially serve as the circuitry of the brain. So, we think, and we think there’s ample evidence to support oligomers as a distinct and uniquely attractive target in this disease, for patients. And what’s also, what was interesting for us having read out the phase one study was, you know, part of the criteria for, Subburnitug is its high selectivity for oligomers versus these other species like monomer or plaques. And so, Subirnatug has at least a somewhat thousand fold selectivity for oligomers versus monomer.

And it’s that distinct ability of Subirnatug to see these oligomers, neutralize them, we think is going to have a beneficial effect in the clinic for patients. In the phase one study, which we undertook exclusively in early Alzheimer’s patients, so they had established amyloid pathology. And as a consequence of being in that disease state, we knew we could interrogate aspects of safety, target engagement, and principally clinical and biomarker effects. And in the in this INTERCEPT AD study, which was designed to help address those early questions in a kind of early derisking of the program, we showed a compelling safety profile. So, there were, you know, the drug was well tolerated.

It had a couple cases of Varia, which we can talk a little bit more about, but was generally well tolerated and, you know, sort of serves as the basis for the safety differentiation that we think Suburbanatog will have. We also showed, target engagement. So, we had a novel assay to, quantify the level of A beta oligomer bound to Subirnatog. And in this assay, we found really a dose response that helped, shape our strategy for phase two. This was actually the first time in the clinic that, actual oligomeric A beta target engagement has been established in a robust way in patients.

So, target engagement, safety, and then much to our encouragement, well, the biomarker effects. We saw with just three administrations of subvertatag, so three doses, we saw amyloid reduction on amyloid PET to the degree and rate similar to like a Lekheme in their CLARITY AD study. So, short duration study, established patient population, we’re seeing, you know, consistent results across a variety of different both fluid and the imaging biomarkers. So, all these to us suggest that a longer duration study such as we’re conducting now with ALTITUDE AD, which is a five forty patient study, two active dose arms versus placebo, intended to read out on a primary outcome of the address, which is a composite score, but then also evaluating the CDR sum of boxes as well as both imaging and fluid biomarkers. You know, we think that study is, well designed and is, you know, ongoing and should be a really impactful outcome for the field to help validate the oligomer hypothesis.

Trung Nguyen, Biopharma Analyst, UBS: Okay. Awesome. Lots to unpack there. Perhaps, why don’t we start on with the biomarker part? For us, actually, I think it’s an area where you’ve shown a lot of data.

You’re, I think, leading the way here in terms of the research for biomarkers and target engagement assays that you’ve done. And you’ve published a lot here. We we’ve seen you’ve recently published this, with that phase one data you discussed. So where do you think we are now with biomarkers? Do you think we’ve got the right biomarkers in place for AD research, or is there still much improvement that’s that’s needed here?

Daniel O’Connor, CEO, Acumen: Well, there’s been a tremendous amount of progress in the development of of fluid biomarkers in particular. Right? If you go back ten or fifteen years, one of the seminal, innovations in the space were the imaging biomarkers. So, we had the ability to use radio labeled, PET tracers to actually image in living patients the presence of of amyloid plaques. Where the field has gotten to now, the fluid biomarkers, including, you know, analytes like, phosphotau two seventeen and one hundred and eighty one and a few others, really provide, greater, you know, consistent resolution and accuracy, but on a less invasive basis, right, rather than radiation exposure and, getting into a pet scanner.

It’s a much more efficient and economical way to prioritize, if not diagnose, patients. And that’s the trend that we foresee, you know, that will continue in the future. The, you know, we’re sort of within the range of a more precision medicine in even Alzheimer’s disease, whereby depending on which of these fluid biomarkers, you may have, it’ll be indicative of disease, etiology and or, state of pathology or state of disease. And this is where those tools being available, more readily available in the clinic, are going to help us identify patients that are best suited for, what we hope will be a number of treatments that come to the clinic over the next three to five years. One of the innovations, you mentioned, you know, we’ve just published the Phase one biomarker paper in J Pad last month.

One of the things that we’ve adopted in the Phase two is using phosphoTAP-two seventeen as essentially part of the screening visit. And there’s enough concordance between, the ratio of two seventeen in plasma to be a reasonable predictor of what the amyloid PET signal is going to look like. So, we’ve been able to use the two seventeen fluid biomarker as a very economical, safe, and efficient path. And I think we’ve presented some of this data, but the negative have been reduced by more than fifty percent as a consequence of that prescreen, you know, giving us, you know, essentially prioritizing those patients that are more likely to be positive in a confirmatory, PET scan.

Trung Nguyen, Biopharma Analyst, UBS: And, you touched upon the potential differentiation in terms of safety that you saw come out of the phase one study. How important do you think are the low rates of ARIA, in the e four homozygous patients. In the phase one, we show you showed no ARIA e amongst a lot of the patients, or the homozygous patients. So just really how important could this be to replicate in your your phase two coming up?

Daniel O’Connor, CEO, Acumen: Yeah. Thanks, Troy. So in in terms of the the safety profile and potential for subunitud, it’s kind of multifactorial because, well, principally because of subveratog’s propensity to bind to oligomers and not plaque, we think that gives it an intrinsic ability to have a lower rate of RAE, in particular. In, it’s also an IgG2, which has a reduced effector function, so that may contribute to lower inflammatory effects and ARIA as well. In the phase one of the forty eight subjects exposed to a dose of Subbertatog, we had five cases of ARIA.

Three were at the high dose of sixty mgs per kg, one was at ten mgs per kg, and one was at twenty five mgs per kg. So, overall, relatively low rate of ARIA. There was only one case deemed to be symptomatic of the five. And so, we think that, again, is a well tolerated, and potential path towards differentiation on safety. We had six E4 homozygotes, none of which developed ARIA even with exposure to drug including some of the higher doses.

So it could be again that because of the epitope and the selectivity for, of Subernatog, it may not see the types of plaques that are resident in, particularly in E4 carriers or E4 homozygous. So it’s an important, facet of of the program and why it’s positioned to succeed. I did want to go back to the the clinical benefits or the the the efficacy question, which we think can be addressed in in phase two, which is one where oligomers, due to that synaptic neurotoxicity, may be a more acute and beneficial way to provide clinical benefit to patients. And precisely how that manifests, you know, we’ll see in the phase two. But there’s, as I mentioned, there’s a tremendous amount of non clinical evidence to suggest that these oligomeric, species are potently toxic and that neutralizing them with a selective agent like Subirnatug should really present as a as a differentiated, efficacy profile.

And that’s really what we’re, you know, all about is is offering a better risk benefit to to patients, relative to the to the first generation products that are now available in the clinic.

Trung Nguyen, Biopharma Analyst, UBS: And moving on to the catalyst that we’re gonna see over the next, year or so, the next big one is the the phase one sub q data. I think top line is fairly soon.

Daniel O’Connor, CEO, Acumen: What should we be looking? Yeah. We’ve run a healthy volunteer phase one study that will read out first quarter of twenty five. So that’s we’re sort of tracking for that, as we sit here today. And then the other, upcoming guidance is the completion of enrollment in altitude AD, which is guided to first half of twenty five.

And I’ll mention that we had our first patient enrolled in altitude AD in May of twenty four. And as I mentioned, this is a two active doses versus, placebo of five forty patients. The study, we’ve noted that the study is enrolled, more quickly or more rapidly than we might have anticipated, which I think is a is a consequence of the greater awareness, just generally of of people, seeking even research options to to be, to prevent the progression of their Alzheimer’s disease. And I also think it’s a consequence of the phase one data that actually provide, you know, a a compelling example of how Subartatog may be a differentiated next generation asset in the, for the treatment of this devastating disease.

Trung Nguyen, Biopharma Analyst, UBS: And digging into that phase two data, which is going to be the big one, you’ve selected thirty five mgs per kg, fifty mgs per kgs, every four weeks. When you look at your PKPD model, do you expect to have a comparable or deeper plaque clearance when you’re comparing that to drugs that are on the market today?

Daniel O’Connor, CEO, Acumen: Well, Jerome, we did for the for the phase two dosing strategy, we did leverage the the phase one target engagement data, which showed essentially a plateauing effect whereby, going higher than sixty mgs per kg was unlikely to produce greater target engagement. And that was a really, again, an important finding in that study to give us confidence that we don’t need to push Subrotatuck higher than sixty mgkg. We also, I mentioned the three cases of ARIA at that sixty mgkg dose. So as a consequence of some PKPD modeling, we elected to take forward fifty mgkg dosing Q4W every four weeks and then thirty five mgkg. And we think that the fifty mgkg dose may yield greater AMLID PET reduction.

It may have a slightly higher rate of ARIA than thirty five mgkg. And the thirty five mgkg may be more of an oligomer centric dosing piece, right? Because you just it may have all of the target engagement but not some of the collateral, plaque effects. But this is why we’re running the study. I mean, both of those dose levels, we think will have, have effects on amyloid plaque.

You know, we are, from a clinical benefit perspective, believe that neutralizing these soluble aggregates, which are distinct from plaque, may actually be, a path towards better treatment for patients. But either of those doses, we think, could be, competitively safe and efficacious. So we’re pretty, we’re very excited to see that study progressing, at the rate it is. And it’ll be, certainly impactful to the field when we’re able to read out altitude AD, in the future.

Trung Nguyen, Biopharma Analyst, UBS: Excellent. And, we’re all looking very much forward to that data. I might be jumping the gun here, but perhaps can you talk about the phase three? Could you incorporate sub q dosing to that study, you know, when we see the data from the sub q top line soon?

Daniel O’Connor, CEO, Acumen: Right. And

Trung Nguyen, Biopharma Analyst, UBS: then go go for it.

Daniel O’Connor, CEO, Acumen: Go ahead. Go ahead.

Trung Nguyen, Biopharma Analyst, UBS: And and then I was I just wanna you know, is is phase three something Acumen is capable doing alone, or should we expect a partnership here?

Daniel O’Connor, CEO, Acumen: Yeah. Well, so on the on the sub q, we’re we’re focused at the in the moment of reading out the top line results, you know, q one here. So that’s gonna be the first next piece of information to to inform the go forward on, on sub q. I think there’s a you know, we we are, you know, there are a variety of different sort of observations or other, approaches people would put forward. We’ll we’ll factor some of those in as to whether or not, you know, when and how we pursue the the sub q based on the the data readout in q one.

And in terms of, you know, the next step for Suburbanatog, I mean, our focus is trying to expedite the advancement of this program for the benefit of patients. So however that comes about and is most beneficial to the pace and, probability of success for Suburbanatog, I think that’s, you know, really where we’re gonna end up for, for phase three and and later stage development.

Trung Nguyen, Biopharma Analyst, UBS: Okay. Excellent. And then the next set of catalysts that you have on the horizon for the year, Last time I spoke to you, there’s you’re keeping very busy this year. We have some conferences in Vienna, Toronto, San Diego. Just what’s the what should we expect from some of these conferences from you guys?

Daniel O’Connor, CEO, Acumen: Yeah. We’ll we’ll be present at, ADPD is the upcoming meeting in in the April in in, Indiana. And then the the, the double a n will be in San Diego later in April, as well. And then we have AIC this year is in in Toronto. So we’ll use those conferences and then CTAD towards the towards the end of the year.

We’ll use each of those, venues and those opportunities to continue to draw attention to, ABLIGOR as a distinct target and the profiling data in support of Subernatog as a next generation, asset in the pursuit of of better treatments for Alzheimer’s patients. So you’ll see, additional some profiling data, some non clinical data, maybe more analyses around some of the biomarker effects in phase one, as well as some of the innovation that we’ve brought to bear in, in phase two, you know, principally around using these fluid biomarkers as a way to streamline drug development and make it more efficient from a cost and convenience standpoint for study participants.

Trung Nguyen, Biopharma Analyst, UBS: Could we see any of the detailed subcu data being presented this year?

Daniel O’Connor, CEO, Acumen: I can’t comment on that, you know, today. I think we’re you know, we’ve got this readout, in this quarter. Yep. It’ll be interesting to see, how that comes together and and what opportunities we have to present in the future.

Trung Nguyen, Biopharma Analyst, UBS: K. Excellent. And,

Daniel O’Connor, CEO, Acumen: I will I guess I I I should comment that, you know, sub queue would be an important and interesting, you know, format for an agent such as Subernatug that there’s obviously, aspects of access and convenience, you know, if, you know, in the right sub q format. So we’re we’re very committed to exploring that option, for Subernatog. I think we do believe that IV and sub q are complementary formats and that, you know, having the agent available in both of those, formats, you know, offers prescribers and patients, choice, which really is helpful, I think, in terms of what is going to be the right option, you know, in a given circumstance, you know, for either a prescriber or a patient.

Trung Nguyen, Biopharma Analyst, UBS: Okay. Understood. And, perhaps following on slightly from the partnership question I asked, have you any thoughts on deal making in this space? It continues to seem quite active to me. We saw AbbVie, by a leader last year.

Just any any thoughts in people’s appetite for CNS and Alzheimer’s disease?

Daniel O’Connor, CEO, Acumen: Yeah. So I would say, Trevor, the the CNS space, you know, given, sort of the early stage risk that the industry has sort of shied away from, does afford, opportunities where, later stage de risked assets, you know, command a lot of attention, and interest from, you know, the established big pharmas that are still still, encouraged or curious to know what, you know, how to play some of these larger neurodegenerative indications. So we think there’s a healthy partnering environment. I think that it just speaks to the unmet need and the promise of, you know, if you have something that is, distinct and, not readily otherwise available, there there’s there’s lots of partnering interest, in the in the CNS space, generally.

Trung Nguyen, Biopharma Analyst, UBS: Excellent. And we’re just heading into the last few minutes here. Do you have any final comments from your side or, what what what message you wanna get out to to anyone that’s listening here today?

Daniel O’Connor, CEO, Acumen: No. Look, we’re we’re really excited to be able to to meet the milestone or the guidance of meeting up sub queue in q one. So that’s, we’re within the zone on that one. And then, it would be even, more exciting for us to to to communicate on the the enrollment milestone. I think that is a significant undertaking to for a relatively small company such as Acumen to go out and enroll five forty patients in a multinational type phase two study is, pretty big lift.

And, I’m encouraged at the progress we’re making and and, just thankful that, you know, we’ve got great study partners, sites, and a team that has been up to the task of, of that effort.

Trung Nguyen, Biopharma Analyst, UBS: Okay. Excellent. Well, thank you so much for your time, Dan. In the next few minutes, we’re gonna have Medicell, present at 1PM. But, again, thanks for your time, and, I hope anyone that listened found that enjoyable.

Thanks. Thanks so much.

Daniel O’Connor, CEO, Acumen: Thank you, Trevor. Take care.

Trung Nguyen, Biopharma Analyst, UBS: Thank you, guys. Bye.

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